Host genetic variation in desmoglein-1 is associated with susceptibility to staphylococcal scalded skin syndrome

Staphylococcal scalded skin syndrome (SSSS), caused by Staphylococcus aureus producing exfoliative toxins, develops in only a subset of colonized children, suggesting host genetic factors may influence disease susceptibility. Desmoglein-1 (DSG1), a key adhesion protein in the superficial epidermis, is the primary target of these exfoliative toxins. This study examined whether genetic variation in the DSG1 gene is associated with SSSS in children.

We conducted a prospective case-control study of children aged 0-5 years, including patients diagnosed with SSSS and age-matched controls who either had non-SSSS S. aureus infections or were asymptomatic carriers, and whose isolates were PCR-confirmed to harbor at least one of the eta and/or etb toxin genes. Genotyping of the DSG1 rs12967407 single nucleotide polymorphism (SNP) was performed using PCR-RFLP.

Eighty SSSS cases and forty controls were enrolled. The C/C genotype was significantly more common in cases than controls (43.8% vs. 12.5%; p = 0.003), whereas the T/T genotype predominated in controls (47.5%) compared to patients (22.5%) (p = 0.006). The C allele was overrepresented among cases (61.3% vs. 32.5%, p < 0.001). Multivariate logistic regression, adjusted for confounders, showed that children with the C/C genotype have a significantly increased risk of developing SSSS (OR = 4.7; 95% CI: 1.3-17.1; p = 0.018).

DSG1-focused genetic profiling may aid in identifying children with heightened susceptibility to SSSS; the rs12967407 C/C genotype confers increased risk for SSSS in children, while the T/T genotype appears to have a protective association.

• Staphylococcal scalded skin syndrome (SSSS) results from S. aureus exfoliative toxins targeting Desmoglein-1; yet interindividual susceptibility varies. • Host genetic factors in SSSS pathogenesis have not been systematically explored.

• This study identifies a significant association between the DSG1 rs12967407 polymorphism and paediatric SSSS. • A significantly increased frequency of the homozygous C/C genotype was detected in SSSS-affected patients, indicating a potential genetic susceptibility. • These findings introduce host genetic variation as a novel determinant in SSSS pathogenesis beyond bacterial virulence.